ArticleGastroenterology2013
Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- A Systematic Review of Genetic Correlates of Weight Loss After Bariatric Surgery.Obesity surgery · 2021Pooled it
- Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial.International journal of obesity (2005) · 2016Trial
- Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis.Cell reports. Medicine · 2026Article
- RYGB induces vagal sensory neuropathy characterized by altered Glp1r expression and enhanced exendin-4 responsiveness in male mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Spontaneous ileitis and postsurgical murine models of enteric hyperoxaluria.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Obesity management for the treatment of type 2 diabetes: emerging evidence and therapeutic approaches.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Gastric bypass alters diurnal feeding behavior and reprograms the hepatic clock to regulate endogenous glucose flux.JCI insight · 2023Article
- Glucose metabolism after bariatric surgery: implications for T2DM remission and hypoglycaemia.Nature reviews. Endocrinology · 2023Review
- Regulation of body weight: Lessons learned from bariatric surgery.Molecular metabolism · 2023Review
- Mechanisms of Weight Loss After Obesity Surgery.Endocrine reviews · 2022Review
- Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats.Frontiers in endocrinology · 2022Article
- Anorexia and Fat Aversion Induced by Vertical Sleeve Gastrectomy Is Attenuated in Neurotensin Receptor 1-Deficient Mice.Endocrinology · 2021Article
- The Phantom Satiation Hypothesis of Bariatric Surgery.Frontiers in neuroscience · 2021Article
- Role of the Autonomic Nervous System in Mechanism of Energy and Glucose Regulation Post Bariatric Surgery.Frontiers in neuroscience · 2021Review
- Do Bariatric Surgeries Enhance Brown/Beige Adipose Tissue Thermogenesis?Frontiers in endocrinology · 2020Review
- Surgical Mouse Models of Vertical Sleeve Gastrectomy and Roux-en Y Gastric Bypass: a Review.Obesity surgery · 2019Review
- Gastric mucosal devitalization improves blood pressure, renin and cardiovascular lipid deposition in a rat model of obesity.Endoscopy international open · 2019Article
- Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats.Molecular metabolism · 2019Article
- Physiological and Epigenetic Features of Yoyo Dieting and Weight Control.Frontiers in genetics · 2019Review
- Roux-en-Y gastric bypass in rat reduces mu-opioid receptor levels in brain regions associated with stress and energy regulation.PloS one · 2019Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsRoux-en-Y gastric bypass (RYGB) improves glucose homeostasis independently of changes in body weight by unknown mechanisms. Melanocortin-4 receptors (MC4R) have weight-independent effects on glucose homeostasis, via autonomic neurons, and also might contribute to weight loss after RYGB. We investigated whether MC4Rs mediate effects of RYGB, such as its weight-independent effects on glucose homeostasis, in mice and humans.
methodsWe studied C57BL/6 mice with diet-induced obesity, MC4R-deficient mice, and mice that re-express MC4R specifically in autonomic neurons after RYGB or sham surgeries. We also sequenced the MC4R locus in patients undergoing RYGB to investigate diabetes resolution in carriers of rare MC4R variants.
resultsMC4Rs in autonomic brainstem neurons (including the parasympathetic dorsal motor vagus) mediated improved glucose homeostasis independent of changes in body weight. In contrast, MC4Rs in cholinergic preganglionic motor neurons (sympathetic and parasympathetic) mediated RYGB-induced increased energy expenditure and weight loss. Increased energy expenditure after RYGB is the predominant mechanism of weight loss and confers resistance to weight gain from a high-fat diet, the effects of which are MC4R-dependent. MC4R-dependent effects of RYGB still occurred in mice with Mc4r haplosufficiency, and early stage diabetes resolved at a similar rate in patients with rare variants of MC4R and noncarriers. However, carriers of MC4R (I251L), a rare variant associated with increased weight loss after RYGB and increased basal activity in vitro, were more likely to have early and weight-independent resolution of diabetes than noncarriers, indicating a role for MC4Rs in the effects of RYGB.
conclusionsMC4Rs in autonomic neurons mediate beneficial effects of RYGB, including weight-independent improved glucose homeostasis, in mice and humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.